The overall goals of the proposed MESA Family Study are to locate and identify genes contributing to subclinical cardiovascular disease (CVD), assessed by coronary calcium (CAC) and carotid intimal medial wall thickness (IMT), and to evaluate the impact of lifestyle and environment on the manifestations of these genetic susceptibilities to CVD in U.S. minority populations. These goals will be addressed in a study of 2700 individuals from 900 sibships (sibtrios), evenly distributed among African-Americans, Hispanic-Americans, and Chinese-Americans, utilizing the existing framework of the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA). In Aim 1, this MESA Family Study will determine the extent of genetic contribution to variation in coronary calcium (EBCT and helical-gated CT scan) and carotid artery intimal-medial thickness (IMT) (B-mode ultrasound) in non-majority U.S. populations. This will be accomplished by phenotyping 1800 siblings of 900 MESA index cases, In Aim 2, using the MESA Study resources (Data Coordination Center, Central Laboratory, CT and Ultrasound Reading Center, 6 Clinical Field Centers), and bringing to bear the combined resources and cardiovascular genetic epidemiology expertise at Cedars-Sinai Medical Center and Wake-Forest School of Medicine, candidate regions in the human genome linked to these quantitative subclinical cardiovascular disease traits (coronary calcium and IMT) will be identified by genome scan approaches. This will be followed by initiation of positional cloning and candidate gene identification within these regions. In Aim 3, we will further pursue gene localization and identification by testing positional and biological candidate genes in both family based and case control association studies. Whereas the purpose of MESA is to assess subclinical CVD and identify risk factors in multi-ethnic populations, the purpose of the MESA Family Study is to identify the genes (quantitative trait loci or QTLs) that contribute to these subclinical CVD risk factors. In combination with traditional risk factor assessment, such inherited markers should be useful in the management of patients with vascular disease, through targeted diagnostic testing and pharmacologic intervention, and in the identification of subjects who could benefit from specific prevention protocols, thus resulting in an increase in the overall well-being of the US population.